Abstract
An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)—a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in the genes responsible for homocysteine metabolism can be perceived to have a greater impact in relation to hyperhomocysteinemia in Indian population. For this reason, the effects of diet and/or methylenetetrahydrofolate reductase (MTHFR) polymorphism were assessed in 200 individuals having varying homocysteine levels. Homocysteine levels were significantly elevated in individuals adhering to a vegetarian diet (P=0.019) or having MTHFR A1298C polymorphism (P=0.006). The minor allele frequency (MAF) of MTHFR C677T and A1298C was 0.15 and 0.44 respectively in this cohort. Since the MAF of these polymorphisms differed considerably from Caucasian and other Asian populations, frequencies of these polymorphisms were also determined in more than 400 individuals from different ethnic populations, selected from the entire country based on their geographical location and linguistic lineage, and was found to be similar to that of our cohort. The fact that MTHFR A1298C polymorphism is significantly associated with homocysteine levels, and that the CC genotype is present at a higher frequency in the Indian population, makes it extremely relevant in terms of its potential impact on hyperhomocysteinemia.
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Acknowledgements
The study was supported in part by funds provided by the Department of Biotechnology, Government of India (SS, GK, and LR) and by the Council of Scientific and Industrial Research under the task force project CMM0016 (SS and SKD). We are also grateful to Prof. S.K. Brahmachari and the entire task force project team (CMM 0016) for valuable inputs and sample collection. We are also grateful to all the faculty members of Department of Cardiology, AIIMS, for consenting to the use of patient data used in the study. We also thank Dr. Dwaipayan Bharadwaj and Dr. Mitali Mukerji for their critical inputs. JK and PS are grateful to the University Grant Commission for their Junior Research Fellowship.
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Kumar, J., Das, S.K., Sharma, P. et al. Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population. J Hum Genet 50, 655–663 (2005). https://doi.org/10.1007/s10038-005-0313-1
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DOI: https://doi.org/10.1007/s10038-005-0313-1
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